α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression
| Autor: | Mari Hayashi, Kenji Fukuzawa, Maeda Shizuka, Kazuho Kamei, Saki Nagao, Kentaro Kogure, Susumu Hama, Yuriko Okamura |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Tocopheryl succinate Angiogenesis alpha-Tocopherol Biophysics Angiogenesis Inhibitors Angiopoietin Biochemistry Neovascularization Angiopoietin-2 03 medical and health sciences Mice Structure-Activity Relationship 0302 clinical medicine medicine.artery Cell Line Tumor Extracellular medicine Angiopoietin-1 Vascular stabilization Animals Humans Molecular Biology Melanoma Aorta Messenger RNA Mice Inbred BALB C Neovascularization Pathologic Chemistry Cell Biology 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Culture Media Conditioned Cancer research Immunohistochemistry medicine.symptom |
| Zdroj: | Biochemical and biophysical research communications. 521(4) |
| ISSN: | 1090-2104 |
| Popis: | α-Tocopheryl succinate (TS) is a tocopherol derivative and has multifaceted anti-cancer effects; TS not only causes cancer cell-specific apoptosis but also inhibits tumor angiogenesis. Although TS has the potential to be used as a well-tolerated anti-angiogenic drug, it is still unclear which step of the angiogenic process is inhibited by TS. Here, we show that TS inhibits the expression of angiopoietin (Ang)-2, which induces destabilization of vascular structure in the initial steps of the angiogenic process. In mouse melanoma cells, TS treatment decreased mRNA and extracellular protein levels of Ang-2; however, the mRNA level of Ang-1, which stabilizes the vascular structure, remained unchanged. Furthermore, aorta ring and Matrigel plug angiogenesis assays indicated that the conditioned medium from TS-treated cells (CM-TS) inhibited neovascularization and blood leakage from the existing blood vessels, respectively. Following immunohistochemical staining of the vessels treated with CM-TS, imaging studies showed that the vascular endothelial cells were highly packed with pericytes. In conclusion, we found that TS inhibits Ang-2 expression and, consequently, stabilizes the vascular structure during the initial step of tumor angiogenesis. |
| Databáze: | OpenAIRE |
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